The Genetics of Rosacea

A new study by researchers from Stanford Medical School and 23andMe is the first to identify genetic variants associated with rosacea, a chronic skin disease estimated to affect more than 16 million people in the United States alone.

Led by Dr. Anne Lynn S. Chang, of Stanford University’s School of Medicine, the study to be published in the Journal of Investigative Dermatology, is the first to identify genetic factors for this common but incurable condition. (The link is to a pre-print version of the paper.) Although the genetic basis for rosacea has long been hypothesized, this is the first study to find genetic variants associated with the condition.

The genes identified in the study support the concept of a genetic basis for rosacea and that could in turn help identify new targets for future studies to better understand and treat this condition.

The discovery portion of the study, which involved the consented participation of more than 22,000 23andMe customers, found two genetic variants strongly associated with the disease among people of European ancestry. Of the 22, 000 customers in this part of the study, more than 2,600 of them had rosacea and the other 20,000 did not have the condition and were used as controls.

Although rosacea is not life threatening, it is a serious and still little understood condition. Some of the symptoms include redness, inflammation, visible blood vessels, pimple like sores on the skin of the central face, as well as burning and itching. Left untreated it can lead to more serious complications, including disfiguring of the nose — called rhinophyma — and damage to the cornea causing vision problems. Because the condition is so visible it can make those who have it feel isolated.

“This is also another example of how 23andMe can help in researching common yet understudied diseases,” said
Joyce Tung, PhD, 23andMe’s Director of Research and a co-author of the paper.

Another intriguing finding from this study is that the single nucleotide polymorphisms (SNPs) found to be strongly associated with the condition, are in or near genes associated with other diseases including diabetes and celiac disease. One of the SNPs found strongly associated with the condition, rs763035, is between the genes HLA-DRA and BTNL2. The HLA-DRA gene is involved in histocompatibility and immune response, which is consistent with the inflammatory nature of rosacea.

To validate the association, 23andMe researchers tested the SNPs from the genome-wide association study in a separate group of 29,000 consented 23andMe customers. The researchers were able to confirm the same association with rosacea. For that portion of the study, researchers looked at more than 3,000 individuals with rosacea and 26,000 controls.

In addition to the genome wide association study that discovered the variants associated with rosacea, Dr. Chang and her team also took skin biopsies from six individuals with rosacea and showed that both HLA-DRA and BTNL2 proteins can be found in the skin of people with rosacea. This preliminary works hints toward the biological relevance of HLA-DRA and BTNL2 in rosacea.

The genetic associations found in this study and the associations with other diseases like diabetes and celiac disease may help direct future study.